The objectives of this Program Project are to determine the qualitative and quantitative alterations in the sex hormone production profiles that occur in postmenopausal women and in aging men. In postmenopausal women, the dominant aspect of the sex hormone production profile is the extraglandular formation of estrone in association with the metabolic changes influencing this process and in association with decreased secretion of estradiol. In aging men, the dominant aspect of the sex hormone production profile is decreased secretion of testosterone in association with increased capacity for extraglandular estrogen formation. Moreover, in aging men and women, extraglandular estrogen formation is increased in the last third of life by obesity, age, and hepatic disease. At the same time, several degenerative or neoplastic diseases occur in hormone target tissues and organs. For example, in postmenopausal women, increased estrone production is associated with the occurrence of endometrial neoplasia. In men, the aging process is associated with prostatic hypertrophy and/or carcinoma. The occurrence of hot flashes at menopause implicates the involvement of the central nervous system and the vasculature. We propose to determine the production rates of sex hormones in postmenopausal women and in aging men and to determine the characteristics of those sex hormone production profiles that affect (1) lipid biosynthesis, (2) endometrial neoplasia and prostatic hypertrophy, (3) neuroendocrine function of the brain (especially the hypothalamus), (4) release of gonadotropins and prolactin, (5) hypertension, and (6) stability of lysosomes in hormone target tissues and organs.